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Breast Cancer Research and Treatment

, Volume 155, Issue 3, pp 483–490 | Cite as

Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor

  • Brandon S. Sheffield
  • Zuzana Kos
  • Karama Asleh-Aburaya
  • Xiu Qing Wang
  • Samuel Leung
  • Dongxia Gao
  • Jennifer Won
  • Christine Chow
  • Rakesh Rachamadugu
  • Inge Stijleman
  • Robert Wolber
  • C. Blake Gilks
  • Nickolas Myles
  • Tom Thomson
  • Malcolm M. Hayes
  • Philip S. Bernard
  • Torsten O. Nielsen
  • Stephen K. L. ChiaEmail author
Clinical trial

Abstract

The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3–5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited.

Keywords

Breast cancer Estrogen receptor Intrinsic subtyping PAM50 Weakly positive ER 

Notes

Acknowledgments

The authors would like to thank the Canadian Breast Cancer Foundation—British Columbia/Yukon chapter for their support of this research. This work was supported by a grant from the Canadian Breast Cancer Foundation (British Columbia and Yukon).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Brandon S. Sheffield
    • 1
  • Zuzana Kos
    • 2
  • Karama Asleh-Aburaya
    • 3
  • Xiu Qing Wang
    • 1
  • Samuel Leung
    • 3
  • Dongxia Gao
    • 3
  • Jennifer Won
    • 3
  • Christine Chow
    • 3
  • Rakesh Rachamadugu
    • 4
  • Inge Stijleman
    • 4
  • Robert Wolber
    • 5
  • C. Blake Gilks
    • 1
    • 3
    • 6
  • Nickolas Myles
    • 1
    • 7
  • Tom Thomson
    • 1
    • 8
  • Malcolm M. Hayes
    • 1
    • 8
  • Philip S. Bernard
    • 4
  • Torsten O. Nielsen
    • 1
    • 3
    • 6
  • Stephen K. L. Chia
    • 1
    • 9
    Email author
  1. 1.Department of Laboratory Medicine and PathologyUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Ottawa and The Ottawa HospitalOttawaCanada
  3. 3.Genetic Pathology Evaluation CentreUniversity of British ColumbiaVancouverCanada
  4. 4.Department of PathologyUniversity of Utah/Huntsman Cancer CenterSalt Lake CityUSA
  5. 5.Department of Laboratory Medicine and PathologyLions Gate HospitalNorth VancouverCanada
  6. 6.Department of Laboratory Medicine and PathologyVancouver General HospitalVancouverCanada
  7. 7.Department of Laboratory Medicine and PathologySt. Paul’s HospitalVancouverCanada
  8. 8.Department of Laboratory MedicineBritish Columbia Cancer AgencyVancouverCanada
  9. 9.Department of Medical OncologyBritish Columbia Cancer AgencyVancouverCanada

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